Treating vasculature related diseases or disorders using nanoparticles

Abstract

The present invention relates to prevention and/or treatment of diseases or disorders associated with a damaged or leaky vasculature in a subject. The present invention provides for methods, combinations and pharmaceutical compositions for preventing and/or treating a disease or disorder associated with a damaged or leaky vasculature in a subject, using, inter alia, an effective amount of a nanoparticle comprising an inner core comprising a non-cellular material, an outer surface comprising a cellular membrane derived from a platelet; and optionally an agent for preventing, treating, diagnosing, or prognosing the disease or disorder and/or monitoring prevention or treatment of the disease or disorder. Exemplary diseases or disorders include hemorrhage (bleeding), cardiovascular diseases or disorders, diseases or disorders associated with narrowing of a blood vessel, tumors or cancers.

The invention claimed is: 
     
       1. A method for preventing and/or treating restenosis associated with a damaged or leaky vasculature in a subject, which method comprises administering, to a subject in need, or to cells of said subject, an effective amount of a nanoparticle comprising a) an inner core comprising a non-cellular material, b) an outer surface comprising a naturally occurring cellular membrane isolated from a platelet; and c) a releasable cargo comprising an agent for inhibiting or reducing tissue growth that contributes to said restenosis,
 wherein said restenosis is coronary restenosis, said agent is docetaxel, and said subject treated with said nanoparticle has intima-to-media ratio (I/M) and/or luminal obliteration that is less than 25% of I/M and/or luminal obliteration of a comparable subject treated with comparable dose of free docetaxel. 
 
     
     
       2. The method of  claim 1 , wherein the inner core comprises a polymeric particle core. 
     
     
       3. The method of  claim 1 , wherein the inner core supports the outer surface. 
     
     
       4. The method of  claim 1 , wherein the cellular membrane comprises a naturally occurring plasma membrane isolated from the platelet. 
     
     
       5. The method of  claim 1 , wherein the nanoparticle has a diameter from about 10 nm to about 10 μm. 
     
     
       6. The method of  claim 1 , wherein the nanoparticle lacks at least 50% of the constituents of the platelet from which the cellular membrane is derived. 
     
     
       7. The method of  claim 1 , wherein the nanoparticle maintains at least 50% of the natural structural integrity or activity of the cellular membrane derived from the platelet or the constituents of the cellular membrane derived from the platelet. 
     
     
       8. The method of  claim 1 , wherein the nanoparticle is biocompatible or biodegradable. 
     
     
       9. The method of  claim 1 , wherein the inner core of the nanoparticle comprises PLGA and the outer surface of the nanoparticle comprises a naturally occurring plasma membrane isolated from the platelet. 
     
     
       10. The method of  claim 1 , wherein the nanoparticle substantially lacks immunogenicity to the subject. 
     
     
       11. The method of  claim 1 , wherein the restenosis is associated with hemorrhage and the nanoparticle further comprises an agent for preventing the hemorrhage, treating the hemorrhage, diagnosing the hemorrhage, prognosing hemorrhage and/or monitoring prevention or treatment of the hemorrhage. 
     
     
       12. The method of  claim 1 , wherein the restenosis is associated with a cardiovascular disease or disorder. 
     
     
       13. The method of  claim 12 , wherein the nanoparticle further comprises an agent for preventing the cardiovascular disease or disorder, treating the cardiovascular disease or disorder, diagnosing the cardiovascular disease or disorder, prognosing the cardiovascular disease or disorder and/or monitoring prevention or treatment of the cardiovascular disease or disorder. 
     
     
       14. The method of  claim 1 , which further comprises administering another active ingredient to the subject. 
     
     
       15. The method of  claim 1 , which further comprises assessing efficacy of the nanoparticle and/or the another active ingredient in preventing and/or treating the restenosis associated with a damaged or leaky vasculature in a subject. 
     
     
       16. The method of  claim 1 , wherein the restenosis is an adverse event of an endovascular procedure. 
     
     
       17. The method of  claim 16 , wherein the endovascular procedure is a vascular surgery, a cardiovascular (heart) surgery or an angioplasty (or balloon angioplasty).